Continuous use of sorafenib will up-regulate the expression of hypoxia-inducible factor 1α (HIF-1α) or hypoxia-inducible factor 2α (HIF-2α), thus promoting the transcription of genes such as mitochondrial phagocytosis, cell proliferation, glucose metabolism, angiogenesis, tumor invasion, and metastasis, and activating the Notch1 signaling pathway, which triggers cell resistance to sorafenib (5). The gene discussed is EPAS1; the disease is neoplasm.